Treatment of fragile x syndrome

Abstract

Described herein is the use of sulindac in the treatment of fragile X syndrome (FXS).

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 62 / 657,209, filed on Apr. 13, 2018, and European Application No. EP18167346.8, filed on Apr. 13, 2018. The entire teachings of the above applications are incorporated herein by reference.FIELD OF THE INVENTION[0002]This invention relates to the use of sulindac in the treatment of fragile X syndrome (FXS).BACKGROUND OF THE INVENTION[0003]Fragile X syndrome, often referred to as fragile X, is the most common inherited cause of intellectual impairment and the most common monogenic cause of autism. It affects around 1 in 4000 males and 1 in 6000 females worldwide.[0004]There are a wide range of characteristics associated with fragile X, and typically males are more affected than females. One of the major characteristics associated with fragile x syndrome is intellectual impairment, such as difficulties with cognitive, executive and language performance. Individuals with f...

AI Technical Summary

Benefits of technology

[0011]In certain embodiments, the present invention relates to sulindac, or a pharmaceutically acceptable salt thereof, for use in the treatment of fragile x syndrome. As will be evident from the in vivo data presented below, sulindac is effective in treating fragile x syndrome. Chronic treatment with sulindac significantly improved the Fmr1 KO2 mouse phenotype, fully rescuing open field and nesting behaviour, while partially rescuing contextual fear conditioning and sociability. This is evidence that sulindac is useful in the therapy of fragile x syndrome.

Problems solved by technology

One of the major characteristics associated with fragile x syndrome is intellectual impairment, such as difficulties with cognitive, executive and language performance.

Individuals with fragile x syndrome typically have social anxiety characterised by social, emotional and communication difficulties related to extreme shyness, poor eye contact and challenges forming peer relationships.

Fragile x syndrome is also associated with hyperactivity and disruptive behaviour, such as short attention span, distractibility, impulsiveness, restlessness, over-activity and sensory problems.

Furthermore, individuals with fragile x syndrome often suffer from seizures.

Once the repeats exceed 200 in number, methylation of the promoter is triggered, and this in turn causes the lack of expression of the gene and translation of its encoded protein, the Fragile X Mental Retardation Protein (FMRP).

At present, there is no effective therapy to treat fragile x syndrome.

Overall, efforts to treat fragile x syndrome have led to some exciting possibilities, but no definitive successes, despite much effort.

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